The cytokine receptor CD27 is a member of the tumor necrosis factor receptor (TFNR) superfamily, which play a role in cell growth and differentiation, as well as apoptosis or programmed cell death. The ligand for CD27 is CD70, which belongs to the tumor necrosis factor family of ligands. CD70 is a 193 amino acid polypeptide having a 20 amino acid hydrophilic N-terminal domain and a C-terminal domain containing 2 potential N-linked glycosylation sites (Goodwin, R. G. et al. (1993) Cell 73:447-56; Bowman et al. (1994) Immunol 152:1756-61). Based on these features, CD70 was determined to be a type II transmembrane protein having an extracellular C-terminal portion.
CD70 is transiently found on activated, but not resting T and B lymphocytes and dendritic cells (Hintzen et al. (1994) J. Immunol. 152:1762-1773; Oshima et al. (1998) Int. Immunol. 10:517-26; Tesselaar et al. (2003) J. Immunol. 170:33-40). In addition to expression on normal cells, CD70 expression has been reported in different types of cancers including renal cell carcinomas, metastatic breast cancers, brain tumors, leukemias, lymphomas and nasopharangeal carcinomas (Junker et al. (2005) J Urol. 173:2150-3; Sloan et al. (2004) Am J Pathol. 164:315-23; Held-Feindt and Mentlein (2002) Int J Cancer 98:352-6; Hishima et al. (2000) Am J Surg Pathol. 24:742-6; Lens et al. (1999) Br J Haematol. 106:491-503). Additionally, CD70 has been found to be overexpressed on T cells treated with DNA methyltransferase inhibitors or ERK pathway inhibitors, possibly leading to drug-induced and idiopathic lupus (Oelke et al. (2004) Arthritis Rheum. 50:1850-60). The interaction of CD70 with CD27 has also been proposed to play a role in cell-mediated autoimmune disease and the inhibition of TNF-alpha production (Nakajima et al. (2000) J. Neuroimmunol. 109:188-96).
Accordingly, CD70 represents a valuable target for the treatment of cancer, autoimmune disorders and a variety of other diseases characterized by CD70 expression.